Perianal Fistula is Complex and Requires Multidisciplinary Management

Combining antibiotics with anti-tumor necrosis factor (TNF) agents has generated superior results in clinical management of perianal fistulizing Crohn disease (CD) and should be encouraged for long-term achievement of clinical remission, according to Millie Long, MD, during her presentation at the Advances in Inflammatory Bowel Disease Regionals virtual regional meeting, September 30.

She also reviewed clinical trial data of the mesenchymal stem cell therapy in the pipeline assessing its safety and efficacy.

Dr Long is a professor of medicine specializing in gastroenterology and hepatology at the University of North Carolina. She is chair of the 2022 AIBD regional meetings.

Her presentation focused on some of the challenges of complex perianal fistulizing CD, including novel medical approaches to treating this disease, whether with antibiotics, conventional therapies, or biologic agents. “It is a complex disorder that requires multidisciplinary management,” Dr Long said.

Speaking about the challenges of fistulas or ‘scars’, she said, “They can recur and may happen at any point in the course of the disease. It results in a poor quality of life for patients and, since there are no clear objective measures of response and remission, they may not respond dramatically to our powerful inflammatory medications.” She added, “Up to 50% of adults with CD will develop a fistula at some point.”

Fistulas could be external (a result of postoperative complications, peri-ileostomy or perianal) or internal (enteroenteric, rectovaginal, or enterovesical). The management of each fistula is different and individual to the type.

External fistulas tends to occur more frequently among patients with colonic inflammation. The rectum is predominantly involved, and therefore, Dr Long strongly recommended that “all patients with inflammatory bowel disease should have a careful perianal and digital rectal exam, with or without symptoms.” For internal fistulas, she recommended ascertaining the severity. If the fistulas are toxic, surgery may be necessary, whereas minimal symptoms may be managed with antibiotics.

Dr Long endorsed each of the 3 most common methods of assessing symptoms—endoscopic ultrasound (EUS), magnetic resonance imaging (MRI), and examination under anesthesia (EUA) noting that all produce excellent results with almost 91% accuracy. “In fact, combining any of these modalities increases the accuracy to 100%, giving doctors a very good idea of the stage and intensity,” she stated.

She also reviewed surgical treatment options in perianal CD. Incision and drainage of abscesses is one of the most common options for noncomplex fistulas. Seton placement encourages drainage of the fistula, which enables healing.

For simple superficial fistulas, fistulotomy can be a good choice, with a healing rate as high as 80-100%; however, she cautions that incontinence may follow this procedure post-treatment.

Ligation of intersphincteric fistula tract (LIFT) has an efficacy rate of 67% but the rate of incontinence is drastically low post-procedure.

Advancement flap is recommended when there is no active proctitis; however, the efficacy rate is 64% and the post-procedure incontinence rate is 9.4%. Diversion, also called proctectomy, still requires some research, as majority of temporary diversions have failed reconnection.

Emphasizing the importance of a multidisciplinary approach, Dr Long clarified that it is not only about a collaboration between gastroenterologists and surgeons, but also about combining antibiotics with anti-TNF therapy. She cited results from a retrospective cohort study in which at both week 12 and week 24, adalimumab and anti-TNF combined gave superior results (71% at week 12 and 62% at week 24) compared to adalimumab with placebo (47% at both week 12 and week 24).

Similarly, combining infliximab with ciprofloxacin 500mg repeatedly gave better results than infliximab combined with placebo. At weeks 8, 12, and 18, infliximab plus ciprofloxacin gave clinical response rates of 90%, 90%, and 70%, respectively, compared to infliximab and placebo, which showed clinical response rates of 60%, 60%, and 40%, respectively.

Another retrospective study indicated week 14 success rate for vedolizumab at 28% vs placebo at 11%; and week 52 success rate for vedolizumab at 31% vs placebo remaining at 11%.

Still, she cautioned, “Steroids are never indicated for perianal fistulas in CD. Steroids, in fact, worsen complications.”

Dr Long is hopeful that mesenchymal stem cell therapy will offer a new option for treatment of for perianal CD once the mechanism clears the ongoing clinical trials and there is more data on the efficacy and safety. It holds promise, she said.

—Priyam Vora

Reference:
Long M. State of the art approach to perianal fistulizing disease. Presented at: Advances in Inflammatory Bowel Disease regional meeting; September 30, 2022. Virtual.